Apparatus and process for encapsulating capsules or other solid dosage forms within capsules

ABSTRACT

The present invention provides an apparatus and process for making softgel capsules having incorporated therein other solid dosage forms selected from the group consisting of pellets, smaller capsules, smaller tablets, sustained release solid dosage forms, immediate release solid dosage forms, extended release solid dosage forms and zero order release solid dosage forms, said apparatus comprising: (a) two spreader boxes; (b) two casting drums; (c) a pair of rotary dies having means for suction; (d) a liquid fill system; (e) a wedge for heating gelatine ribbons and feeding said fill; and (f) two lateral dispensing devices said lateral dispensing devices including hoppers having said solid dosage forms, channelguides for transporting said solid dosage forms and a grasping claw for dispensing said solid dosage form into the softgel pocket formed in the rotary dies.

This application is a continuation of US application Ser. No. 13/137,045filed Jul. 18, 2011; now U.S. Pat. No. 8,967,989 issued Mar. 3, 2015,the entire contents of which are incorporated by reference. Thisapplication also claims the priority benefit under 35 U.S.C. section 119of U.S. Provisional Patent Application No. 61/344,416 entitled“Apparatus And Process For Encapsulating Capsules Within Capsules” filedJul. 19, 2010, which is in its entirety herein incorporated byreference.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for the production ofsoft gelatin capsules containing internally other solid dosage forms orsmaller capsules within said capsules. The capsules of the invention arenow well established as a means for providing a variety of liquidproducts such as drugs and dietary supplements in a readily ingestibleform especially when two drugs are not compatible with each other.

This invention further relates to softgels (or soft gelatin capsules)containing one or more smaller capsules within such capsules and to aprocess and apparatus for the manufacture thereof. The present inventionalso relates to a gelatin capsule of the soft type containing multipleactive ingredients or the like, and more particularly to a novel gelatincapsule capable of containing multiple medicines or dietary supplementas the content separated from each other, and its manufacturing methodand manufacturing apparatus.

The present invention also relates generally to a method and apparatusfor forming capsules within capsules containing a measured amount of notcompatible medicinals and more particularly to a method and apparatusfor forming capsules. The method and apparatus of the present inventionare particularly useful in connection with forming softgel capsuleshaving other solid dosage forms containing multiple pharmaceuticalproduct, such as for example medicines, vitamins, food supplements andthe like which are not compatible with each other.

The present invention further relates to encapsulation machines and,more particularly, to soft encapsulation machines which make softgelatin capsules having other smaller capsules within or other soliddosage form.

The invention is particularly useful for making formulations wherein twoactive ingredients are not compatible with each other but it isdesirable to administer them in the same dosage form i.e., a capsulewithin a capsule or another solid dosage form within a capsule.

BACKGROUND OF THE INVENTION AND DESCRIPTION OF THE PRIOR ART

The art of encapsulation has been known for many years, particularly forthe production of unit dosage forms containing various pharmaceuticalproducts. Normally, such pharmaceutical capsules are composed of gelatinor some modification thereof, which is fabricated essentially into twodifferent forms, namely, the so-called hard gelatin capsule and the softgelatin capsule.

It is also known that conventional soft gelatin capsules are a preferredfrom of administration for medicaments and similar products; especiallyliquids, pastes, solids dispersed in liquids, or dry solids. Softgelatin capsules also possess particular advantages for substances whichrequire total protection from air and light, because the gelatin iscompletely sealed around the contents. An important example is for theencapsulation of vitamins, which has resulted in a high degree ofstability thereof.

Hard gelatin capsules are also known in the art, and are generallyformed from two distinct parts, namely the “cap” and the “body”, fittingone into the other so as to form the complete capsule. The cap and thebody are manufactured by the same process consisting of immersing in agelatin solution the end of a mandrel whose form corresponds to theinner volume of the cap or of the body, then withdrawing the mandrelfrom the solution and letting the layer of gelatin thus deposited dry,which is then removed like a glove finger. Hard shell capsules so formedhave problems of leakage and do not provide adequate protection from airand light

Soft gelatin capsules, now more commonly known as softgels, have beenwell known and widely used for many years. Softgels generally comprisean outer shell primarily made of gelatin, a plasticizer, and water, anda fill contained within the shell. The fill may be selected from any ofa wide variety of substances that are compatible with the gelatin shell.Softgels are widely used in the pharmaceutical industry as an oraldosage form containing many different types of pharmaceutical andvitamin products. In addition to use as an oral dosage form for drugsand vitamins, soft gelatin capsules or softgels are also designed foruse as suppositories for rectal or vaginal use. Other uses are fortopical and ophthalmic preparations and the like. The cosmetic industryalso uses softgels as a specialized package for various types ofperfumes, oils, shampoos, skin creams and the like. Softgels areavailable in a great variety of sizes and shapes, including roundshapes, oval shapes, oblong shapes, tube shapes and other special typesof shapes such as stars. The finished capsules or softgels can be madein a variety of colors. Also, opacifiers may be added to the shell.

The process for making softgel capsules includes the step wherein thegelatin shell and the fill material come together to form Softgelcapsules. It takes place in a closed environment called clean room wherethe relative humidity is around 20%. The gelatin shell and fill materialare brought together simultaneously in the encapsulation machine.

The process is basically performed as follows: a pump delivers the warmgelatin over two chilled drums which are located at both opposite sidesof the machine, through a spreader box that sits over each drum. Thewarm liquid gelatin flows over the drums and this transforms the liquidgelatin into two solid ribbons of gel. The left and right ribbons passover rollers which feed them through two die rolls. These die rollsdetermine the shape and size of softgels and cut the Softgel shell fromthe ribbons as they turn around.

Simultaneously, a sensitive and high accuracy positive displacement pumpdelivers the fill material into a heated wedge which sits between rotarydies. This wedge injects the fill material into the die cavities betweenribbons just right before the die rolls cut the ribbons and seal the twohalves together. Warm just formed softgels slide gently through a chuteonto a conveyor belt which carries them to the tumble dryer wherecooling and drying process takes place.

In more specific detail, typical soft encapsulation machines form atleast two flexible gelatin sheets or ribbons by cooling molten gelatinon separate drums then lubricating and guiding the sheets intocommunication with each other over co-acting dies while simultaneouslydispensing a desired quantity of fill material between the sheets insynch with cavities in the outer surfaces of the dies to produce softcapsules. The encapsulation machines typically utilize gearing tocontrol the relative rotations of the various components and fillmechanisms to synchronize the operation of these various components. Thesynchronization of these various components, however, can vary dependingupon a variety of factors, such as the particular dies used, the numberof cavities and the size of the cavities on the dies, and the type ofmaterial used to form the sheets. To change the synchronization of thevarious components, mechanical gears are required to be changed toobtain the desired ratios and synchronization of these components. Thechanging of gears, however, is time intensive. Additionally, the use ofmechanical gears provides finite gear ratios which limit thesynchronization of the various components to the mechanical gears thatare available. Thus, it would be advantageous to provide a capsulemachine wherein the synchronization and rates at which the variouscomponents operate can be altered without the necessity of changinggears. Additionally, it would be advantageous if the synchronizationbetween the various components can be infinite to thereby allow moreprecise synchronization between the various components. It would also beadvantageous to allow various components, such as the fill mechanism, tobe adjusted independently of the other components while the machine isrunning to allow for adjustments of the timing of fill material insertedinto each of the soft capsules. It would also be advantageous toeliminate the use of casting drums in the making of softgel capsules.

During the operation of the capsule making machine, the contact betweenthe adjacent dies can be adjusted by the operator of the capsule makingmachine. Typically, the operator is able to move one of the dies closerto the other die so that the pressure or force exerted on the sheetspassing between the adjacent dies can be adjusted. Such adjustments,typically are mechanical adjustments made by fluid actuators, such aspneumatic cylinders. The operator is able to adjust the pneumaticpressure thereby altering the force the dies exert on one another and onthe sheets. This adjustability allows an operator to customize thepressure to ensure that quality soft capsules are produced. However, thedies are susceptible to premature failure and/or wear when the pressureor force between the two dies is more than that required to produceacceptable soft capsules. Thus, it would be advantageous tomonitor/record the pressure applied to the dies so that quality capsulesare produced without inducing excessive wear or premature wear on thedies.

A material fill mechanism is used to supply the fill material that isencapsulated within the soft capsules. When the fill material is aliquid, such as a liquid medication or die for a paint ball capsule, thefill mechanism includes a plurality of positive displacementplunger-type pumps that are arranged in a housing above the dies. Theplunger-type pumps are positioned on a yoke that moves linearly in areciprocating motion to allow the plunger-type pump to fill with theliquid fill material on one stroke and subsequently discharge the liquidfill material on the other stroke. A valving arrangement betweenopposing pumps is utilized to control the discharge and filling of thepumps. The valve arrangement includes a sliding member that moveslinearly back and forth in a direction generally perpendicular to thelinear motion of the yoke. The discharge of the liquid fill materialinto the sheets as they are passing through the dies is coordinated withthe operation of the dies to insure that the timing of the injection ofthe liquid fill material is synchronized with the cavities on the dies.Typically, this synchronization has been performed through the use ofmechanical gears that link the timing of the stroke to the rotation ofthe dies. Thus, in order to adjust the synchronization a mechanical gearchange is required which is time consuming. Additionally, the timing islimited to a finite number of gear ratios as determined by the gearsthat are available.

The sliding member of the valving mechanism requires lubrication.Typically, the lubrication is provided by a lubricating pump with itsown separate drive. However, the use of a separate drive to operate thelubricating pump adds additional complexity and components to thecapsule machine. Thus, it would be advantageous if a motion of the slidemember and/or the yoke could be utilized to drive the lubrication pump.

The pumps are typically contained within a housing that is filled with alubricating oil that is used to lubricate the sliding member. The pumps,however, can leak around their seals and contaminate the lubricating oilwith the leaking fill material. Contamination of the oil requires a timeconsuming and possibly difficult clean up and can cause the lubricatingoil to not perform as designed thereby increasing the wear on thesliding surfaces and decreasing the life span of the sliding surfaces.Thus, it would be advantageous to capture any fill material that leaksfrom the pumps and deter or prevent the liquid fill material fromcontaminating the lubricating oil within the pump housing.

The pumps are typically driven by a drive mechanism that is also locatedwithin the pump housing. Because the drive mechanism is located in thepump housing, it is possible for liquid fill material that leaks fromthe pumps to contaminate not only the lubrication oil but also the drivemechanism. When switching from one fill material to another, the pumpand all of the components in the pump housing are required to bethoroughly cleaned to remove all contamination. The locating of thedrive mechanism within the pump housing provides additional componentsthat must also be cleaned when changing the fill material. Thus, itwould be advantageous to separate the drive mechanism from the pumphousing to reduce the components that are required to be cleaned whenchanging fill material.

The soft capsules produced by the encapsulation machine are transportedfrom the encapsulation machine to a dryer to additionally dry the softcapsules and to make them into final form. The soft capsules aretransported from the encapsulation machine to the dryer by a conveyorthat extends along the front of the encapsulation machine. The conveyorcan be contaminated by the fill material during operation of theencapsulation machine. When it is desired to switch the product beingproduced on the encapsulation machine, the conveyor must be removed fromthe encapsulation machine and cleaned to remove any contaminatesthereon. The conveyor is driven by a motor that is attached to theconveyor. When it is necessary to remove the conveyor for cleaning, themotor must also be taken with the conveyor which makes it more difficultto remove and transport the conveyor and requires additional time todisconnect the motor from the encapsulation machine. The presentinvention provides an encapsulation machine that overcomes theabove-described disadvantages of typical encapsulation machines.

Applicant is aware of the following publications briefly discussedbelow. U.S. Pat. No. 1,970,396 features a method and machine forproducing soft gelatin capsules in an automated process. The methodinvolves the formation of two gelatin sheets or films through the use ofa gravity fed spreader box, cooling the liquid gelatin on two separatewebs, then lubricating and guiding the two sheets into communicationwith each other between two co-acting dies while simultaneouslydispensing the proper amount of medicine or other filling materialbetween the sheets in registration with half cavities in the outersurface of the dies.

U.S. Pat. No. 5,761,886 discloses an apparatus for forming capsules thatprovides rotary dies that are independently moveable and the ability tovary the speed of the dies during the formation of a single capsule. The'886 device also utilizes independently controlled casting drums toreduce “set-up” time and provide better quality control. Even though the'886 patent discloses a very sophisticated encapsulation machine, itstill utilizes a gravity fed spreader box for formation of theencapsulating ribbon.

Other patents relating to encapsulation techniques which disclose theuse of spreader boxes to create the film or ribbon on a casting druminclude U.S. Pat. Nos. 2,288,327; 2,774,988; 5,246,638; 5,735,105; and6,022,499.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view of the complete apparatus of the inventionshowing all the elements of the apparatus.

FIG. 2 is also a front view of the apparatus of FIG. 1 without thespreader boxes and casting drums.

FIG. 3 is a front view of the mechanism for filling the capsules withother capsules.

FIG. 4 is also a front view of how the smaller capsules are dispensedinto the larger capsule.

FIG. 5 shows the smaller capsule hopper having capsules which are fedvia guiding channels into the larger capsule.

FIG. 6 shows a representative end product of the invention containingtwo capsules inside another capsule.

FIG. 7 are representative examples of products contemplated by theinvention.

SUMMARY OF THE INVENTION

The present invention responds specifically to the long-felt needheretofore unmet by the prior art, and especially with a view toovercoming the inherent inadequacies of combination of pharmaceuticalsthat are not compatible for oral delivery to mammals. The composition isa pharmaceutical combination i.e., a capsule within a capsule providingthe convenience and reliability of oral administration, while providingnear simultaneous delivery in vivo of incompatible substances. Thecomposition is shelf stable when formulated.

The foregoing, and other advantages of the present invention, arerealized in one aspect thereof in an oral pharmaceutical compositionthat is a combination of incompatible active ingredients. Thecomposition comprises a double soft capsule which includes onepharmaceutical in a first capsule which is enclosed second soft capsulealso containing a second active ingredient. The soft capsules arepreferably made of gelatin. The active ingredients may be combined withacceptable grade carriers.

In another aspect, the invention is a method of simultaneouslydelivering incompatible compounds to mammals in vivo. Such delivery isachieved by administering orally to a mammal a double soft capsulecontaining a first substance in a first capsule, which is enclosed witha second substance, incompatible with the first substance, in a secondlarger soft capsule. In another embodiment, this invention provides amethod for preparing shelf-stable compositions of incompatiblesubstances, which includes the use of multiple capsules of variablecomposition. Such method is accomplished manually or by the apparatus ofthe invention further described below.

As used herein, the term “incompatible” is meant to refer to substanceswhich deleteriously react with one another when combined in desiredlevels or concentrations.

The invention also provides an apparatus for making softgel capsuleshaving incorporated therein other solid dosage forms selected from thegroup consisting of pellets, smaller capsules, smaller tablets,sustained release solid dosage forms, immediate release solid dosageforms, extended release solid dosage forms and zero order release soliddosage forms, said apparatus comprising: (a) two spreader boxes; (b) twocasting drums; (c) a pair of rotary dies having means for suction; (d) aliquid fill system; (e) a wedge for heating gelatine ribbons and feedingsaid fill; and (f) two lateral dispensing devices said lateraldispensing devices including hoppers having said solid dosage forms,channelguides for transporting said solid dosage forms and a graspingclaw for dispensing said solid dosage form into the softgel pocketformed in the rotary dies.

The invention further provides a dispensing device for dispensing andfeeding solid dosage forms into a softgel capsule said dispensing andfeeding device including a hopper having said solid dosage forms,channelguides for transporting said solid dosage forms and a graspingclaw for dispensing said solid dosage form.

The instant invention also provides a method for making softgel capsuleshaving incorporated therein other solid dosage forms, said methodcomprising: casting a gel forming composition to make films; (b) passingsaid films through a pair of rotary dies having vacuum means to makepockets; (c) feeding smaller solid dosage forms into said pockets usinga lateral dispensing and feeding system that uses a grasping claw; (d)filling said pockets with a medicine formulation in liquid form via awedge segment; and (e) forming said capsule by sealing the pocketstogether.

The invention is also a process for making a softgel capsule havingincorporated therein another capsule, said process comprising: (a)feeding film sheets between a first die roll and a second die rollwherein each of the die rolls have capsule pockets in a plurality ofrows and said capsule pockets have at least one orifice for applicationof suction; (b) applying suction while said film is in place in thecapsule pockets; (c) feeding via guidechannels through a lateraldispensing device having a hopper and a grasping claw preformed smallercapsules onto the film sheets overlying the die rolls at positionshaving the capsule pockets; (d) filling said capsule pockets also via awedge segment with a liquid medical formulation; and (e) cutting thefilm sheets about the capsule pockets to form said soft gel capsuleshaving capsules in combination with a suitable liquid pharmaceuticalcombination.

The invention further provides softgel capsules incorporated into anouter softgel capsule, tablets incorporated into an outer softgelcapsule, microgranules incorporated into an outer softgel capsule, andany combination between softgels, tablets and/or microgranulesincorporated into an outer softgel capsule.

The instant invention also provides a softgel capsule havingincorporated therein another solid dosage form selected from the groupconsisting: (a) one capsule contains an omega oil and the other soliddosage form is a capsule having a statin; (b) one capsule contains anon-steroidal antiinflammatory and the other solid dosage form containsand antihistamine; and (c) one capsule contains and omega oil and theother solid dosage form contains a salicylate.

Other advantages and a fuller appreciation of the specific adaptations,compositional variations, and physical and chemical attributes of thepresent invention will be gained upon an examination of the followingdetailed description of the invention, taken in conjunction with theaccompanying drawings and appended claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an innovative and efficient system forthe manufacture of capsules with two or more internal components.Although the internal components may be incompatible the invention isalso intended to provide internal components that are compatible but areintended to be released at different intervals.

The present invention provides an advanced drug delivery system thatplaces different pharmaceuticals forms in a single dosage combination.The invention allows delivering incompatible pharmaceutical actives inthe form of solid, liquid, microgranules, gels, hard shell or soft gelcapsules within an outer softgel capsule.

The novel dosage system allows for combining different therapeuticentities that have never been combined before, via oral, ovules, orsuppositories.

For the multi-drugs regimen patients and due to the incompatibility ofsome actives that can not be combined in a single dose, the instantinvention offers a universe of possibilities for current and future newdrugs combinations and supplies different releasing delivery.

In the present invention, existing and proven delivery systems arecombined in a highly reliable, easy to use and affordable manufacturethat give the resulting dosage form unique characteristics to deliversingle or multiple APIs regardless of physical-chemical compatibilityand/or stability liabilities.

For the multi-drugs regimen patients this delivery system is a viablealternative; due to the manufacturing of IR plus MR combinations intablets and hard-gelatin capsules while enhancing dosing accuracy andby-passing dissolution barriers and coating issues. It allows theformulation of combination products, highly needed to assure patientcompliance and allow synergic clinical effects in a safe and stabledosage form.

Some of the most important advantages are:

Fast and sustained release in a single dose.

Gastric or intestinal release in the same dose.

Fewer intakes to be administered.

Simplicity of regimen reduces mistakes.

Impossible to be falsified.

Reduces number of Rx's prescribed by Physician.

Smaller number of presentations to maintain.

The invention further provides soft-gelatin capsules as aimmediate-release (IR) delivery system, that upon rupture, it releasesimmediate or modified release (MR) tablets, capsules, softgels, granulesand/or microgranules. Compatible and/or incompatible pharmaceuticalactive ingredients, and/or blends of IR and MR dosage forms of the sameor different active pharmaceutical ingredients (APIs) can be dosedsimultaneously in a single capsule. These capsules may be designed to beadministered orally, vaginally or rectally, as needed.

Referring in detail to the apparatus shown in FIG. 1, reference numeral1 illustrates a medicine hopper having a cover 2 and a medicine feeder 3connected with a clamp. The apparatus further includes a medicinedistributor system 4, pump 5 to pump medicine and further includesplunger 6. The apparatus also includes a fitting distributor connection7, medicine tubing/hoses 8, a segment coupling connection 9, a supportsegment 10, and wedge segment 11.

The apparatus has lateral hoppers 12 and 13 containing smaller capsulesor other solid dosage forms that are intended to be encapsulated by thesoft gels being formed in the rotary dies. The lateral hopper dispensingsystem includes acrylic or other material knob fasteners 14 and acrylicsubstrate 15 having guide channels/tracks 16 for the smaller capsules orother smaller solid dosage forms such pellets or minitablets, etc. Thelateral dispensing system of the invention includes a grasping claw 17for dispensing the smaller capsules coming through channels/track 16.The apparatus further includes the conventional aspects of makingsoftgel capsules which includes a gelatin film 18, guiding rollers 19,tensioner 20, rotary mold 21, a vacuum system 22, capsule exit 23 afterthe capsule is formed, a yoke support arm 24, housing 25, spreader geldispensing boxes and casting drum 27.

FIG. 2 illustrates the apparatus of FIG. 1 without the spreader geldispensing boxes and casting drums. The reference numerals in FIG. 2 areidentical as those in FIG. 1.

The film-forming materials of the invention comprise at least onecomponent selected from the group consisting of gelatin, starch,carrageenans, gums or synthetic materials such ashydroxypropyl-methylcellulose (HPMC), other hydroxyalkylated cellulosesand the like. The film-forming material typically has an aqueous baseand is considered to be ingestible. As used herein, the term“ingestible” is used to indicate a film-forming material that dissolvesunder conditions simulating the human digestion tract or water.

FIG. 3 shows the dispensing and feeding of solid dosage forms orcapsules that come from hoppers 12 and 13 (not shown-See FIGS. 1 and 2)controlled by grasping claw 17 with volume capacity for accurate dosingfixed within the capsule. The smaller dosage form or smaller capsules isfed through guide channels 16 and deposited inside a half pocket as thesoftgel capsule is being formed in rotary die 21. The grasping claw 17releases each capsule into each packet as the rotary die moves. Thefinal capsule is also filled with additional pharmaceutical actives inliquid form injection tubing 8. After filling the formed capsule 23falls-through to a conveyor belt and then transported for drying.

FIG. 4 further illustrates in more details the feeding of solid dosageforms or capsules into the rotary molding process for making softgelcapsules containing internally other dosage forms such as smallercapsules, pellets, small tablets, etc. The feeding of the internalcapsule is made by an independent dispenser having guide channels 16 sothat as capsules are deposited in the pocket of the rotary die/mold 21,the wedge segment 11 is used to simultaneously dispense a liquidmedicine product to fill the capsule. As is well known gelatin film 18is used to form the softgel pocket in the rotary die/mold 21.

FIG. 5 shows one of the lateral hoppers having smaller solid dosageforms or smaller capsules to be filled inside another softgel capsule.The hopper 12 having capsules 13, are released from the hopper anddeposited and guided through guidechannels 16 which in turn leads to thepocket in the rotary mold that is in a tangential position.

FIG. 6 illustrates a finished capsule of the invention. One or moresmaller capsules may be encapsulated in any way into another immersed ina liquid or solution containing a pharmaceutical active ingredient.

The resulting products of the invention include softgel capsules havingincorporated therein another solid dosage form selected from the groupconsisting: (a) one capsule contains an omega oil and the other soliddosage form is a capsule having a statin; (b) one capsule contains anon-steroidal antiinflammatory and the other solid dosage form containsand antihistamine; and (c) one capsule contains and omega oil and theother solid dosage form contains a salicylate.

Typically the omega oil is an omega-3 oil and the statin is selectedfrom the group consisting of mevastatin, lovastatin, pravastatin,fluvastatin, simvastatin, rosuvastatin, cerivastatin and atorvastatinand derivatives and analogs thereof.

The non-steroidal antiinflammatory acid is selected from the groupconsisting of ibuprofen, naproxen, benoxaprofen, flurbiprofen,fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen, carprofen,oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen,tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac,tolmetin, zomepirac, diclofenac, fenclofenac, alclofenac, ibufenac,isoxepac, furofenac, tiopinac, zidometacin, acemetacin, fentiazac,clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid,niflumic acid and tolfenamic acid, diflunisal, flufenisal and piroxicam.

The antihistamine is selected from the group consisting ofdiphenhydramine, loratadine, cetirizine, fexofenadine, hydroxyzine,cyproheptadine, chlorphenamine, clemastine and desloratadine.

The salicylate is typically acetylsalicylic acid.

The present invention provides delivery systems which are combined in ahighly reliable, easy to use and affordable manufacture that give theresulting dosage form unique characteristics to deliver single ormultiple APIs regardless of physical-chemical compatibility and/orstability liabilities. The soft-gelatin delivery system can be filledwith hydrophilic or lipophilic media to suspend various IR and/or MRdosage forms in drug solutions or plain liquid phases.

The delivery system of the invention is a viable alternative to themanufacturing of IR plus MR combinations in tablets and hard-gelatincapsules while enhancing dosing accuracy and by-passing dissolutionbarriers and coating issues. It also solves compatibility and stabilityissues for multivitamins, cold remedies, nutraceuticals and multipleother OTC medications. The invention also allows the formulation ofcombination products, highly needed to assure patient compliance andallow synergistic clinical effects in a safe and stable dosage form.

The invention also allows for ease of identification by color coding theshell, fill and/or contents minimizing counterfeiting risks.

The contents of my non-provisional applications filed Jul. 18, 2011, andconcurrently filed with this application and based on provisionalapplication Nos. 61/344,417 and 61/344,416 are incorporated by referencein their entirety as if they were individually denoted.

All patents, patent applications and publications cited in thisapplication including all cited references in those applications andpublications, are hereby incorporated by reference in their entirety forall purposes to the same extent as if each individual patent, patentapplication or publication were so individually denoted.

While the many embodiments of the invention have been disclosed aboveand include presently preferred embodiments, many other embodiments andvariations are possible within the scope of the present disclosure andin the appended claims that follow. Accordingly, the details of thepreferred embodiments and examples provided are not to be construed aslimiting.

It is to be understood that the terms used herein are merely descriptiverather than limiting and that various changes, numerous equivalents maybe made without departing from the spirit or scope of the claimedinvention.

The invention claimed is:
 1. A dispensing and feeding device fordispensing and feeding solid dosage forms into a softgel capsule, saiddispensing and feeding device including a hopper having said soliddosage forms, channelguides for transporting said solid dosage forms,and a grasping claw for dispensing said solid dosage forms, eachgrasping claw having volume capacity for grasping a fixed dose of thesolid dosage forms coming through one of the said channelguide andconfigured for releasing the fixed dose into a pocket of the softgel. 2.A method for making softgel capsules having incorporated therein othersolid dosage forms, said method comprising: (a) casting a gel-formingcomposition to make films; (b) passing said films through a pair ofrotary dies having vacuum means to make pockets of a softgel capsule;(c) feeding via channelguides smaller solid dosage forms into saidpockets using a lateral dispensing and feeding system that uses graspingclaws, each grasping claw having volume capacity for grasping a fixeddose of the solid dosage forms coming through one of said channelguidesand configured for releasing the fixed dose into a pocket of the softgelcapsule; (d) filling said pockets with a medicine formulation in liquidform via a wedge segment; and (e) forming said softgel capsule bysealing the pockets together.
 3. A process for making a softgel capsulehaving incorporated therein one or more smaller capsules, said methodcomprising: (a) feeding film sheets between a first die roll and asecond die roll wherein each of the die rolls have capsule pockets in aplurality of rows and said capsule pockets have at least one orifice forapplication of suction; (b) applying suction while said film sheets arein place in the capsule pockets; (c) feeding preformed one or moresmaller capsules onto the film sheets overlying the die rolls atpositions having the capsule pockets via channelguides through a lateraldispensing device having a hopper and grasping claws, each grasping clawhaving volume capacity for grasping a fixed dose of the preformedsmaller capsule coming through one of said channelguides and configuredfor releasing the fixed dose into a capsule pocket; (d) filling saidcapsule pockets also via a wedge segment with a liquid medicalformulation; and (e) cutting the film sheets about the capsule pocketsto form said softgel capsules having the one or more smaller capsules incombination with the liquid medical formulation.